hematopoietic system
• at day 6 after PI-PC treatment, mutant mice show impaired erythropoiesis in bone marrow and spleen; a 4-fold reduction of mature erythroid cells is noted in speen
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• both mutant and control mice show a 25% reduction in hematocrit levels at 6 days after PI-PC treatment; however, control animals are able to normalize this defect 1 week later, whereas mutant mice remain anemic
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• adult mutant mice exhibit impaired megakaryopoiesis and erythropoiesis with loss of early progenitor cells in both lineages
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• mutants display a 50% reduction in total bone marrow cellularity relative to control mice
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• megakaryocytes from mutant bone marrows are larger (~2-fold increase in diameter) and appear dysplastic with hyperlobulated nuclei
• megakaryocytes are virtually absent from the spleens of mutant mice; however, megakaryocytes in deleted bone marrows retain the ability to shed platelets in response to thrombocytopenia
• in mutant bone marrow, CFU-S12 colonies are reduced 2-fold and appear smaller and pale with no erythroid or megakaryocytic component
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• in vitro, mutant bone marrows and spleens are devoid of megakaryocyte progenitors
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• at 6 days after PI-PC treatment, mutant bone marrows and spleens are devoid of erythroid progenitors (BFU-E)
• in contrast, the frequency and behavior of myeloid CFCs is not significantly affected
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• after 6 days and 3 injections of PI-PC, mutant mice continue to display decreased platelet counts whereas increased megakaryocytopoiesis in the spleen has normalized platelet counts in control mice
• notably, mutant mice do recover completely from the acute fall in their white cell count
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• megakaryocytes are virtually absent from the spleens of mutant mice
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immune system
• megakaryocytes are virtually absent from the spleens of mutant mice
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skeleton
• flushed bone marrow samples from mutant mice are pale relative to control samples
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